6-116500620-T-G

Position:

• chr6-116500620-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001139444.3(TRAPPC3L):​c.287A>C​(p.Asn96Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TRAPPC3L NM_001139444.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.96

Genes affected

TRAPPC3L (HGNC:21090): (trafficking protein particle complex subunit 3L) Predicted to be involved in endoplasmic reticulum to Golgi vesicle-mediated transport and intra-Golgi vesicle-mediated transport. Part of TRAPP complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11352378).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRAPPC3L	NM_001139444.3	c.287A>C	p.Asn96Thr	missense_variant	4/5	ENST00000368602.4	NP_001132916.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRAPPC3L	ENST00000368602.4	c.287A>C	p.Asn96Thr	missense_variant	4/5	5	NM_001139444.3	ENSP00000357591.3
TRAPPC3L	ENST00000437098.5	c.245A>C	p.Asn82Thr	missense_variant	3/4	3		ENSP00000395769.1
TRAPPC3L	ENST00000356128.4	c.35A>C	p.Asn12Thr	missense_variant	2/3	2		ENSP00000348445.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 01, 2023

The c.287A>C (p.N96T) alteration is located in exon 4 (coding exon 4) of the TRAPPC3L gene. This alteration results from a A to C substitution at nucleotide position 287, causing the asparagine (N) at amino acid position 96 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.035	.;.;T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.084
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.52	T;T;T
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.11	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	.;.;L
MutationTaster	Benign	0.99	N;N
PrimateAI	Benign	0.39	T
PROVEAN	Benign	0.86	N;N;N
REVEL	Benign	0.036
Sift	Uncertain	0.027	D;D;D
Sift4G	Benign	0.14	T;T;T
Polyphen		0.012	.;.;B
Vest4		0.27
MutPred		0.46		.;.;Gain of sheet (P = 0.0827);
MVP		0.099
ClinPred		0.31	T
GERP RS		2.9
Varity_R		0.16
gMVP		0.11

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-116821783;